Hydrogen peroxide-induced oxidative damage and apoptosis in cerebellar granule cells: Protection by Ginkgo biloba extract

The ability of oxidative stress to induce apoptosis and the protective effe cts of Ginkgo biloba extract (EGb761) against this induction were studied i n cultures of rat cerebellar granule cells. Cells were exposed to oxidative stress by treatment with 50 mu M hydrogen peroxide + 100 mu M ferrous sulp hate which generates hydroxyl radicals by Fenton reaction. Both morphologic al observation and biochemical analysis revealed that H2O2/FeSO4 treatment induced apoptotic cell death in cerebellar granule cells, which was charact erized by chromatin condensation and DNA fragmentation. During this process , the fluidity of the cell membrane decreased markedly, and the conformatio n of membrane proteins altered significantly. Pretreating cerebellar granul e cells with the antioxidant EGb761 (Ginkgo biloba extract) effectively att enuated oxidative damage induced by H2O2,/FeSO4 and prevented cells from ap optotic cell death. The results suggested that EGb761 might be used as a po tential drug for neuronal diseases associated with the excessive production of reactive oxygen species. (C) 2000 Academic Press.